Devices to resist migration and rotation of implants used in brachytherapy and other radiation therapy

ABSTRACT

An anchor mechanism includes a sleeve to fit around a structure such as a radioactive source, a thermal ablation implant, a spacer, a strand or a radiopaque marker. The sleeve has a bore that extends an entire longitudinal length of the sleeve, and through which the structure fits, such that the structure can extend out from both longitudinal ends of the sleeve. One or more protrusion extends from an outer surface of the sleeve to engage surrounding patient tissue after implantation of the structure into a patient, to thereby reduce a tendency for the structure to migrate and rotate after implantation.

PRIORITY CLAIM

This application is a continuation-in-part (CIP) of U.S. patentapplication Ser. No. 11/187,411, filed Jul. 22, 2005, and entitledIMPLANTS FOR USE IN BRACHYTHERAPY AND OTHER RADIATION THERAPY THATRESIST MIGRATION AND ROTATION, which is incorporated herein byreference.

FIELD OF THE INVENTION

This invention relates to radiotherapy. More particularly, it relates toimplants for use in brachytherapy, and in particular to therapeuticmembers, spacers and strands that are used to resist migration androtation of radioactive sources. The invention also relates toimplantable radiopaque markers that resist migration and rotation.

BACKGROUND

Brachytherapy is a general term covering medical treatment whichinvolves placement of radioactive sources near a diseased tissue and mayinvolve the temporary or permanent implantation or insertion ofradioactive sources into the body of a patient. The radioactive sourcesare thereby located in proximity to the area of the body which is beingtreated. This has the advantage that a high dose of radiation may bedelivered to the treatment site with relatively low doses of radiationto surrounding or intervening healthy tissue. Exemplary radioactivesources include radioactive seeds, radioactive rods and radioactivecoils.

Brachytherapy has been used or proposed for use in the treatment of avariety of conditions, including arthritis and cancer. Exemplary cancersthat may be treated using brachytherapy include breast, brain, liver andovarian cancer and especially prostate cancer in men. For a specificexample, treatment for prostate cancer may involve the temporaryimplantation of radioactive sources (e.g., rods) for a calculatedperiod, followed by their subsequent removal. Alternatively, theradioactive sources (e.g., seeds) may be permanently implanted in thepatient and left to decay to an inert state over a predictable time. Theuse of temporary or permanent implantation depends on the isotopeselected and the duration and intensity of treatment required.

Permanent implants for prostate treatment include radioisotopes withrelatively short half lives and lower energies relative to temporaryseeds. Exemplary permanently implantable sources include iodine-125,palladium-103 or cesium-131 as the radioisotope. The radioisotope can beencapsulated in a biocompatible casing (e.g., a titanium casing) to forma “seed” which is then implanted. Temporary implants for the treatmentof prostate cancer may involve iridium-192 as the radioisotope. Fortemporary implants, radioactive rods are often used.

Conventional radioactive seeds are typically smooth sealed containers orcapsules of a biocompatible material, e.g., titanium or stainless steel,containing a radioisotope within the sealed chamber that permitsradiation to exit through the container/chamber walls. Other types ofimplantable radioactive sources for use in radiotherapy are radioactiverods and radioactive coils, as mentioned above.

Preferably, the implantation of radioactive sources for brachytherapy iscarried out using minimally-invasive techniques such as, e.g.,techniques involving needles and/or catheters. It is possible tocalculate a desired location for each radioactive source which will givethe desired radiation dose profile. This can be done using knowledge ofthe radioisotope content of each source, the dimensions of the source,accurate knowledge of the dimensions of the tissue or tissues inrelation to which the source is to be placed, plus knowledge of theposition of the tissue relative to a reference point. The dimensions oftissues and organs within the body for use in such dosage calculationsmay be obtained prior to or during placement of the radioactive sourcesby using conventional diagnostic imaging techniques including X-rayimaging, magnetic resonance imaging (MRI), computed tomography (CT)imaging, fluoroscopy and ultrasound imaging.

During the placement of the radioactive sources into position, a surgeoncan monitor the position of tissues such as the prostate gland using,e.g., ultrasound imaging or fluoroscopy techniques which offer theadvantage of low risk and convenience to both patient and surgeon. Thesurgeon can also monitor the position of the relatively large needleused in implantation procedures using ultrasound or other imaging.

Once implanted, radioactive sources (e.g., seeds, rods or coils) areintended to remain at the site of implantation. However, the radioactivesources may on some occasions migrate within a patient's body away fromthe initial site of implantation. This is undesirable from a clinicalperspective, as migration may lead to underdosing of a tumor or otherdiseased tissue and/or exposure of healthy tissue to radiation.Additionally, there have been reported incidents where a migrated seedimplant has caused a pulmonary embolism. Accordingly, there is a need toreduce the tendency for radioactive sources to migrate within apatient's body.

Radioactive sources may also on some occasions rotate or twist from theoriginal orientation at which the seed was implanted. This is alsoundesirable from a clinical perspective, because the radiation patternof the sources may be directional, thereby causing underdosing oroverdosing of a tumor or other diseased tissue and/or exposure ofhealthy tissue to radiation. Accordingly, there is also a need to reducethe tendency for radioactive sources to rotate within a patient's body.

Efforts have been made to reduce the tendency for radioactive seeds tomigrate within a patient's body. For example, U.S. Pat. No. 6,632,176discloses a radioactive seed having a biocompatible container with atleast one part of a surface of the container being roughened, shaped orotherwise treated so that it is no longer smooth. According to the '176patent, the roughening, shaping or other treatment is achieved by:forcing the seed container through a ridged or serrated dye or athreading device to impart grooves on the outer surface of thecontainer; milling the seed container; using a wire brush, file, orsandpaper to roughen the outer surface of the container; etching using alaser or water-jet cutter, or by electrolytic etching; blasting (e.g.,sand blasting); or electroplating.

Disadvantages of the radioactive seeds disclosed in the '176 patent isthat they are not off the shelf seeds, but rather, are custom seedswhose manufacturing cost is likely higher than that of a typicalradioactive seed. Additionally, even though the '176 patent says thatthe treatment process should not compromise the integrity of thecontainer, the integrity of the container may indeed be affected by theroughing, shaping and other treatments suggested in the '176 patent.Additionally, because the containers themselves are being changed, theradioactive seeds having such roughened, shaped or otherwise treatedcontainers may be subject to government certification orre-certification. Further, the modified containers may affect thedirectional radiation pattern of the seed, potentially resulting inadverse clinical results. Accordingly, it is preferred that the means ofreducing the tendency for radioactive seeds to migrate and/or rotatewithin a patient's body overcome the above mentioned disadvantages.

When performing external beam radiation procedures such as intensitymodulated radiation therapy (IMRT) and conformal radiation therapy (CRT)it is important that a target for radiation be accurately identified. Toaccomplish this, radiopaque markers (sometime referred to as fiducial orfiduciary markers) are often implanted into the patient at or near thetarget, so that the radiation can be accurately focused. Once implanted,such markers are intended to remain at the site of implantation.However, the markers may on some occasions migrate and/or rotate withina patient's body away from the initial site of implantation. This isundesirable because it is the locations of the markers that are used todetermine where to focus the radiation treatments. Accordingly, there isa need to reduce the tendency for such markers to migrate and/or rotatewithin a patient's body.

SUMMARY OF THE INVENTION

Embodiments of the present invention are directed to therapeutic membersand strands for use in brachytherapy. Such members and strands, as willbe understood from the detailed description, are designed to reduce thetendency for the members and strands (and thus the radioactive sourcestherein) to migrate and/or rotate within a patient's body.

In one embodiment a member includes a radioactive source and a materialthat encapsulates the radioactive source. Such encapsulating material,which is preferably, but not necessarily, bioabsorbable, is likelypolymeric or some other plastic material. An outer surface of theencapsulating material includes at least one protrusion, and preferablya plurality of protrusions, to reduce the tendency of the member tomigrate and rotate within a patient's body after implantation.

In accordance with an embodiment, one or more of the protrusions extendin a radial direction (e.g., perpendicular or at an acute angle) withrespect to a longitudinal axis of the radioactive source. One or moreprotrusions may also extend in a longitudinal direction with respect tothe radioactive source. Such protrusions can have various shapes, suchas, but not limited to, square, rectangular, circular, oval, triangular,pyramidal and semi-spherical, or combinations thereof.

In accordance with an embodiment, the one or more protrusions includeone or more ribs that form one or more rings or a helix about a radialcircumference of the radioactive source.

In accordance with another embodiment, the plurality of protrusionsforms an irregular pattern on the outer surface of the encapsulatingpolymeric material. For example, the plurality of protrusions can form asurface that resembles a rough stucco surface.

In another embodiment, the encapsulating material is used to form ananchor mechanism that extends from at least one of the longitudinal endsof the radioactive seed to reduce a tendency of the member to migrateand rotate within a patient's body after implantation. In accordancewith an embodiment, a void is formed between the anchor mechanism andthe portion of the material that encapsulates the radioactive source, toallow patient tissue to enter the void after implantation.

Embodiments of the present invention are also directed to spacers, whichare used to separate radioactive sources from one another, wherein thespacers include protrusions and/or anchor mechanisms, similar to thosedescribed above.

Embodiments of the present invention are also directed to strands thatinclude protrusions and/or anchor mechanisms, similar to those describedabove. Such strands include a plurality of radioactive sources that arespaced apart from one another at desired intervals.

Embodiments of the present invention are also directed to spacers andstrands that include portions that are biased to open afterimplantation, to thereby engage surrounding tissue.

Embodiments of the present invention are also directed to radiopaquemarkers that include protrusions and/or anchor mechanisms, similar tothose described above, to reduce the tendency of the markers to migrateand rotate within a patient's body after implantation.

Embodiments of the present invention are also directed to an anchormechanism that includes a sleeve to fit around a structure, such as aradioactive source, a thermal ablation implant, a spacer, a strand or aradiopaque marker. One or more wing is connected to the sleeve by acorresponding living hinge that enables the wing to be folded againstthe structure during implantation of the structure in a patient. Theliving hinge biases the wing such that one end of the wing moves awayfrom the structure to engage surrounding patient tissue afterimplantation of the structure into a patient. This engagement of thewing with the tissue reduces a tendency for the structure to migrate androtate after implantation.

Embodiments of the present invention are also directed to an anchormechanism that includes a sleeve to fit around a structure, such as aradioactive source, a thermal ablation implant, a spacer, a strand or aradiopaque marker. The sleeve has a bore that extends an entirelongitudinal length of the sleeve, and through which the structure fits,such that a portion of the structure can extend out from eachlongitudinal end of the sleeve. One or more protrusion extends from anouter surface of the sleeve to engage surrounding patient tissue afterimplantation of the structure into a patient, to thereby reduce atendency for the structure to migrate and rotate after implantation.

This summary is not intended to be a complete description of theinvention. Other features, aspects, objects and advantages of theinvention can be obtained from a review of the specification, thefigures, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a side view of a therapeutic member according to anembodiment of the present invention; and FIG. 1B is a perspective viewof the therapeutic member shown in FIG. 1A.

FIGS. 2-5 are side views of therapeutic members according to variousembodiments of the present invention.

FIG. 6A is a side view of a therapeutic member according to a furtherembodiment of the present invention; and FIG. 6B is a perspective viewof the therapeutic member shown in FIG. 6A.

FIG. 7A is a side view of a therapeutic member according to anotherembodiment of the present invention; and FIG. 7B is a perspective viewof the therapeutic member shown in FIG. 7A.

FIG. 8A is a side view of a member with tabs; FIG. 8B is a perspectiveview of the member shown in FIG. 8A; FIG. 8C is a side view of thetherapeutic member of FIGS. 8A and 8B after the tabs have been shapedinto anchor mechanisms; FIG. 8D is a perspective view of the membershown in FIG. 8C; and FIG. 8E is an end view of the therapeutic membershown in FIGS. 8C and 8D.

FIG. 9 is a side view of an exemplary applicator that can be used toimplant therapeutic members of the present invention into a patient'sbody.

FIG. 10A is a perspective view of a spacer according to an embodiment ofthe present invention, in an open position; FIG. 10B is a perspectiveview of the spacer in FIG. 10A in a closed position; and FIG. 10C is aperspective view of the spacer of FIGS. 10A and 10B in a partiallyopened position.

FIG. 11 is a side view of a strand according to an embodiment of thepresent invention.

FIG. 12 is a side view of a strand according to another embodiment ofthe present invention.

FIG. 13 is a perspective view of a strand that includes portions whichare biased to open after implantation, and thereby engage tissuesurrounding the strand, to prevent migration and rotation of the strand.

FIG. 14A is a side view illustrating an anchor mechanism according to anembodiment of the present invention, it its closed position; FIG. 14B isa perspective view of the anchor mechanism of FIG. 14A, in its closedposition; FIG. 14C is a side view of the anchor mechanism of FIGS. 14Aand 14B, in its open position; and FIG. 14D is a perspective view of theanchor mechanism of FIGS. 14A-C, in its open position.

FIG. 15A is a side view illustrating an anchor mechanism according toanother embodiment of the present invention. FIG. 15B is a perspectiveview of the anchor mechanism of FIG. 15A.

FIG. 15C is a side view illustrating an anchor mechanism according to afurther embodiment of the present invention. FIG. 15D is a perspectiveview of the anchor mechanism of FIG. 15C.

DETAILED DESCRIPTION

Embodiments of the present invention relate to therapeutic members foruse in treatments such as brachytherapy. As shown in FIGS. 1A and 1B,each member 100 includes a radioactive source 102 (shown in dashed line)and a material 104 that encapsulates the radioactive source 102. Theradioactive source 102 can be a radioactive seed, a radioactive rod, ora radioactive coil, but is not limited thereto. The material 104 ispreferably, but not necessarily, bioabsorbable. In accordance with anembodiment, the material 104 is also bioadherent. Additionally, thematerial 104 is preferably a polymeric material or some other plastic.Also shown in FIG. 1 is that an outer surface of the encapsulatingmaterial 104 includes protrusions 106 to reduce a tendency of the member100 to migrate and rotate within a patient's body after implantation.Also shown in FIG. 1B (in dotted line) is a longitudinal axis of theradioactive source 102, which is also the longitudinal axis of thetherapeutic member 100. The overall shape of the therapeutic member 100,excluding the protrusions 106, can be cylindrical with flat ends 120 and122, cylindrical with rounded (e.g., bullet shaped) ends 120 and 122 orrectangular, but is not limited thereto.

The protrusions that are used to reduce a tendency of the member tomigrate and rotate can be of any number of different shapes and sizes,or combinations thereof. For example, in FIGS. 1A and 1B the protrusions106 are shown as being square or rectangular knobs that cause the outersurface of the therapeutic member 100 to resemble a knobby tire. Theprotrusions 106 can form a plurality of rows (e.g., four rows) which areregularly spaced about the member 100, e.g., with each row extending ina direction that is 90 degrees from the adjacent rows. Alternatively,the protrusions can protrude in a more random or irregular fashion.

Exemplary dimensions for one of the protrusions 106 in FIG. 1B is shownas being 0.010×0.008×0.003 inches. All of the protrusions 106 can havesimilar dimensions, or the dimensions of the protrusions may vary. Forexample, it is possible that the protrusions within a row have similardimensions, but the dimensions differ for different rows. For a morespecific example, another row of protrusions 106 have dimensions of0.006×0.005×0.002 inches. These are just a few examples. One of ordinaryskill in the art will appreciate from this description that theprotrusions can have other dimensions while being within the scope ofthe present invention.

Preferably, the protrusions extend at least 0.002 inches so that theycan sufficiently grip into patient tissue (analogous to a knobby tiregripping soft dirt). The protrusions 106 can extend radially from thetherapeutic member 100. For example, in the embodiments shown, theprotrusions 106 extend in directions that are generally perpendicular tothe longitudinal axis 103 of the therapeutic member 100 and the source(e.g., seed) 102 therein. The protrusions 106 may alternatively oradditionally extend at other angles with respect to the longitudinalaxis 103. For example, protrusions may extend at 45 degrees with respectto the longitudinal axis 103. In a specific embodiment, each half of themember 100 can have protrusions 106 at a 45 degree angle facing towardsthe middle of the member 100, or towards the ends of the member 100.Various other angles, and combinations of angles, are also possible.

In FIGS. 1A and 1B, and FIGS. 2-5 discussed below, the protrusions areshown as extending from the length of the therapeutic member. However,the protrusions may also extend from the longitudinal ends of thetherapeutic member.

In another embodiment, shown in FIG. 2, the protrusions 206 of atherapeutic member 200 are cylindrical. In still another embodiment,shown in FIG. 3, a therapeutic member 300 includes protrusions 306 thatresemble bumps or semi-spheres. In the embodiment shown in FIG. 4 theprotrusions 406 of a therapeutic member 400 are triangular, and in theembodiment of FIG. 5 the protrusions 506 of a therapeutic member 500 arepyramidal. These are just a few examples of the shapes of theprotrusions. One of ordinary skill in the art reading this descriptionwould appreciate that other shapes are also possible. It should also beunderstood that a therapeutic member of the present invention caninclude protrusions of numerous different shapes, including, but notlimited to, the shapes shown in FIGS. 1-5. While in the FIGS. thevarious protrusions are shown as having a common orientation, it is alsowithin the scope of the present invention that the protrusions havedifferent orientations. For example, in FIG. 5, different triangularprotrusions 506 can have different orientations.

In a further embodiment, shown in FIGS. 6A and 6B, the protrusions areribs 608 that encircle the underlying source 102. Four ribs 608 areshown in FIGS. 6A and 6B. However, it should be understood that more orless ribs 608 can be included. It should also be understood the ribs canbe helical (i.e., spiral). In one specific embodiment, the ribs can formcounter balancing screw threads (i.e., opposing helixes). For example,the threads on one half of the member can be right hand threads, whilethe threads on the other half of the member can be left hand threads.

In another embodiment, the plurality of protrusions can form anirregular pattern on the outer surface of the encapsulating polymericmaterial 104. For example, the protrusions can form what resembles arough stucco like surface, e.g., as shown in FIGS. 7A and 7B.

In the embodiments where the radioactive sources 102 are radioactiveseeds, the seeds 102 can be of various types having low energy and lowhalf-life such as Iodine seeds, known as I-125 seeds, including a weldedtitanium capsule containing iodine 125 adsorbed on a silver rod, orPalladium 103 seeds. Seeds may also have there isotope adsorbed onceramic beads, resin beads, silver beads, graphite pellets, porousceramic rods, copper cores, etc. Seed can have various different shapes,such as, but not limited to, cylindrical with flat ends, cylindricalwith rounded (e.g., bullet shaped) and spherical. Exemplary dimensionsof a seed 102 are 0.18 inches in length and 0.0315 inches in diameter.Exemplary seeds are listed below in Table 1, but embodiments of thepresent invention should not be limited to the seeds listed therein.

TABLE 1 Seed Manufacturers and Common Types of Seeds MANUFACTURER SEEDNAME IODINE¹²⁵ Amersham 6711 OncoSeed Amersham 6733 EchoSeed Amersham7000 RAPID Strand North American Scientific IoGold Best Industries BESTIodine-125 Bebig Symmetra Mills Biopharmaceuticals ProstaSeed SyncorPharmaSeed International Isotopes IsoStar Implant Sciences I-PlantInternational Brachytherapy InterSource-125 IsoAid Advantage I-125Source Tech STM1251 DRAXIMAGE, Inc. BrachySeed PALLADIUM¹⁰³ NorthAmerican Scientific Pd Gold Theragenics Theraseed 200 Best IndustriesBEST Palladium-103 International Brachytherapy InterSource 103

Alternatively, seeds 102 can be manufactured using iridium 192, cesium131, gold 198, yttrium 90 and/or phosphorus 32. Further radioactiveisotopes used to manufacture seeds are not limited to these examples,but can include other sources of different types of radiation.

In addition it is to be understood that other types of seeds can beused. For example, seeds such as those described in U.S. Pat. No.6,248,057, which is incorporated herein by reference, can be used withthe present invention. These seeds include radiation delivery devices,drug delivery devices, and combinations of radiation and drug deliverydevices in the form of beads, seeds, particles, rods, gels, and thelike. These particular seeds are absorbable wherein the radiation memberor drug delivery member is contained within, for example, absorbablepolymers such as those listed below or in the above-referenced patent.In such seeds, the bioabsorbable structure can have a predefinedpersistence which is the same as or substantially longer than a halflife of the radioactive member contained in the bioabsorbable structure.These above bioabsorbable seeds can be used in the same manner as theseeds described herein with respect to the invention. As mentionedabove, the radioactive sources 102 need not be seeds. For example, theradioactive sources 102 can be rods, e.g., metallic rods coated with aradioactive isotope such as palladium 103, etc. The radioactive sources102 may also be radioactive coils, such as those described in U.S. Pat.No. 6,419,621, which is incorporated herein by reference, and thoseavailable from RadioMed Corporation of Tyngsboro, Mass., under thetrademarks GENETRA and RADIO COIL. In accordance with an alternativeembodiment, rather than using a radioactive source, an implant thatutilizes thermal ablation to treat cancer can be used. One such implant,which is marketed under the trademark ThremoRod, and is available fromAblation Technologies of San Diego, Calif., is a permanently implantablecobalt-palladium alloy rod that produces heat (e.g., 70 degrees C.)through oscillation of a magnetic field. In such embodiments, thematerial 104 is used to encapsulate the thermal ablation implant and toform protrusions, as described above, to resist migration and rotationof the implant.

To allow X-ray detection of the radioactive sources, the radioactivesources can include a radiopaque marker, which is typically made of adense, high atomic number material, such as gold or tungsten, which canblock the transmission of X-rays so that the radioactive source can bedetected by using X-ray imaging techniques. This can be accomplished,e.g., by including a ball, rod or wire constructed of a dense, highatomic number material, such as gold or tungsten, within the containerof a radioactive source (e.g., seed). Alternatively, the radioactiveseed (or other source) can be at least partially coated with aradiopaque material.

The therapeutic members of the present invention can be manufactured invarious manners. For example, a molding process, such as compressionmolding or injection molding can be used. In one example, a radioactivesource is placed into an embossing mold that includes the inverse (i.e.,negative) of the pattern of projections that is to be embossed on theouter surface of the polymeric material. Before or after the source(e.g., seed) is placed in the mold, a bioabsorbable polymer or someother plastic material is introduced into the mold at a temperature thatis above the melt point of the material such that the material flowsaround the seed within the mold cavity. The material is then allowed toset within the mold, e.g., by cooling the mold. After the material hasset, the mold is opened, and the finished therapeutic member with aplurality of polymeric projections is removed. In other embodiments, anencapsulating material is molded around the seed, and then theprotrusions are produced in a secondary process, e.g., by machining,crimping or otherwise altering the shape of the encapsulating materialto form protrusions. In still other embodiments, the protrusions areformed in the encapsulating material prior to the seed being placed intothe material. In still further embodiments, the protrusions can bedoughnut shaped pieces that are slid over the radioactive sourceimplant. These are just a few examples. Other techniques for producingthe protrusions are also within the scope of the present invention.

For the embodiment of FIGS. 7A and 7B, where the outer surface or themember 700 resembles a rough stucco surface, a mold can includepurposeful protrusions, or can simply be a rough surface that was formedwhen casting or otherwise manufacturing the mold. Typically, the metalof the mold would be machined such that a member produced using the moldwould have a generally smooth surface. However, in accordance with anembodiment of the present invention the mold is left rough, so that themember 700 formed using the mold would have random protrusions.

In another embodiment, a radioactive source 102 is encapsulated within apolymeric material, and then protrusions are attached to the outersurface of the encapsulating material in a secondary process. Forexample, while the outer surface of the encapsulating material is tacky,particles or strands can be attached to the outer surface to therebyform the protrusions. The outer surface of the encapsulating materialcan be made tacky by heating the material, coating the material with abiocompatible adhesive, or otherwise wetting the material. The particlesor strands can then be attached to the outer surface of the material,e.g., by sprinkling the particles or strands onto the outer surface, orrolling the encapsulated source in the particle or strands. Suchparticles or strands should be biocompatible, and can alsobioabsorbable. The particle or strands can be made of the same materialas the material 104 that encapsulates the radioactive source 102, butthis is not necessary. It is also possible that the container of theradioactive source be coated with a biocompatible adhesive, and that theparticles or strands are directly attached to the container of theradioactive source, to thereby form the protrusions that resistmigration and rotation.

In another embodiment, the material 104 can be molded or otherwiseformed around a source 102 such that a tab 808 extends longitudinally(i.e., axially) from each longitudinal end of the encapsulatedradioactive source 102, as shown in FIGS. 8A and 8B. In a secondaryprocess, each tab 808 is heated and formed into an anchor mechanism 810,shown in FIGS. 8C and 8D. More specifically, the main body of the member800 (within which the seed 102 is located) can be held in place whileeach tab 808 is melted into a desired shape by pushing against the tab808 with a heated surface or mold that is moved toward the main body ofthe member. The heated surface or mold that is used to melt the tab 808can simply be a flat surface, which will cause the anchor mechanism 810to have an amorphous shape. Alternatively, the mold that is used to meltthe tab 808 can be shaped to cause the anchor mechanism 810 to have aspecific shape, such as a square, as shown in FIGS. 8C and 8D. FIG. 8E,which is an end view of the member 800 shown in FIGS. 8C and 8D,includes exemplary dimensions in inches.

In FIGS. 8C-8E, the anchor mechanism 810 is square shaped. Inalternative embodiments the anchor mechanisms can have other shapes. Forexample, the anchor mechanism 810 can be amorphous, rectangular,triangular, trapezoidal, etc. In accordance with specific embodiments,an outer surface 812 of the anchor mechanism 810 is generallyperpendicular to the longitudinal axis 103 of the radioactive source102, as shown in FIGS. 8C and 8D. A void or groove 814 is formed betweenthe main portion of the member and the anchor mechanism 810, therebyallowing patient tissue to occupy this void 814 to reduce the tendencyfor the member 800, and the radioactive source 102 therein, to migrateor rotate.

It is preferred that the anchor mechanism 810 be located at eachlongitudinal end of the therapeutic member 800, as shown in FIGS. 8C and8D. However, in alternative embodiments the anchor mechanism 810 can belocated at only one of the longitudinal ends of the member. In FIGS.8A-8E the outer surface of the main body of the therapeutic member 800is shown as being generally cylindrical and smooth. However, this neednot be the case. The embodiments of FIGS. 1-7 discussed above can becombined with the embodiments of FIGS. 8A-8E. For example, a same moldthat is used to form the protrusions of FIGS. 1-7 can be used to formthe tabs 808, which can then shaped into the anchor mechanisms 810 in asecondary process after the members have been removed from the mold. Instill another embodiment, the anchor mechanisms 810 can be formed by anembossing mold similar to that used to form the protrusions of FIGS.1-7.

The radioactive sources 102 can be coated with or contain a drug and/orhormone. Alternatively, a drug and/or hormone can be included in theencapsulating material 104 that is used for form the protrusions oranchor mechanisms of the present invention.

Example types of materials 104 that are bioabsorbable include, but arenot limited to, synthetic polymers and copolymers of glycolide andlactide, polydioxanone and the like. Such polymeric materials are morefully described in U.S. Pat. Nos. 3,565,869, 3,636,956, 4,052,988 andEuropean Patent Publication No. 0030822, all of which are incorporatedherein by reference. Specific examples of bioabsorbable polymericmaterials that can be used to produce the therapeutic members ofembodiments of the present invention are polymers made by Ethicon, Inc.,of Somerville, N.J., under the trademarks “MONOCRYL” (polyglycoprone25), “MAXON” (Glycolide and Trimethylene Carbonate), “VICRYL”(polyglactin 910) and “PDS II” (polydioxanone).

Other exemplary bioabsorbable materials include poly(glycolic acid)(PGA) and poly(-L-lactic acid) (PLLA), polyester amides of glycolic orlactic acids such as polymers and copolymers of glycolate and lactate,polydioxanone and the like, or combinations thereof. Such materials aremore fully described in U.S. Pat. No. 5,460,592 which is herebyincorporated by reference. Further exemplary bioabsorbable polymers andpolymer compositions that can be used in this invention are described inthe following patents which are hereby incorporated by reference: U.S.Pat. No. 4,052,988 which discloses compositions comprising extruded andoriented filaments of polymers of p-dioxanone and 1,4-dioxepan-2-one;U.S. Pat. No. 3,839,297 which discloses compositions comprisingpoly[L(−)lactide-co-glycolide] suitable for use as absorbable sutures;U.S. Pat. No. 3,297,033 which discloses the use of compositionscomprising polyglycolide homopolymers as absorbable sutures; U.S. Pat.No. 2,668,162 which discloses compositions comprising high molecularweight polymers of glycolide with lactide; U.S. Pat. No. 2,703,316 whichdiscloses compositions comprising polymers of lactide and copolymers oflactide with glycolide; U.S. Pat. No. 2,758,987 which disclosescompositions comprising optically active homopolymers of L(−) lactidei.e. poly L-Lactide; U.S. Pat. No. 3,636,956 which disclosescompositions of copolymers of L(−) lactide and glycolide having utilityas absorbable sutures; U.S. Pat. No. 4,141,087 which discloses syntheticabsorbable crystalline isomorphic copolyoxylate polymers derived frommixtures of cyclic and linear diols; U.S. Pat. No. 4,441,496 whichdiscloses copolymers of p-dioxanone and 2,5-morpholinediones; U.S. Pat.No. 4,452,973 which discloses poly(glycolic acid)/poly(oxyalkylene) ABAtriblock copolymers; U.S. Pat. No. 4,510,295 which discloses polyestersof substituted benzoic acid, dihydric alcohols, and glycolide and/orlactide; U.S. Pat. No. 4,612,923 which discloses surgical devicesfabricated from synthetic absorbable polymer containing absorbable glassfiller; U.S. Pat. No. 4,646,741 which discloses a surgical fastenercomprising a blend of copolymers of lactide, glycolide, andpoly(p-dioxanone); U.S. Pat. No. 4,741,337 which discloses a surgicalfastener made from a glycolide-rich blend of polymers; U.S. Pat. No.4,916,209 which discloses bioabsorbable semi-crystalline depsipeptidepolymers; U.S. Pat. No. 5,264,540 which discloses bioabsorbable aromaticpolyanhydride polymers; and U.S. Pat. No. 4,689,424 which disclosesradiation sterilizable absorbable polymers of dihydric alcohols. Ifdesired, to further increase the mechanical stiffness of the moldedembodiments of the present invention, bioabsorbable polymers and polymercompositions can include bioabsorbable fillers, such as those describedin U.S. Pat. No. 4,473,670 (which is incorporated by reference) whichdiscloses a composition of a bioabsorbable polymer and a fillercomprising a poly(succinimide); and U.S. Pat. No. 5,521,280 (which isincorporated by reference) which discloses bioabsorbable polymers and afiller of finely divided sodium chloride or potassium chloride.

The final hardness of a polymer of the therapeutic members of thepresent invention should preferably be in a range from 20 to 80durometer and more preferably in the range of 20-40 durometer. However,members with other hardnesses are also within the scope of the presentinvention. Where the material 104 is bioabsorbable, the bioabsorbablematerial should preferably be absorbed in living tissue in a period oftime of from about 70 to about 120 days, but can be manufactured to beabsorbed anywhere in a range from 1 week to 1 year or more, depending onthe therapeutic plan for a specific patient. The material 104 shouldalso be biocompatible, whether or not it is bioabsorbable. The material104 may also be bio-adhesive.

In accordance with an embodiment of the present invention, the minimumthickness of the material 104 that encapsulates the source 102 should beabout 0.002 inches. Such minimum thickness would occur at locationswhere there is not a protrusion. The preferred thickness of the material104 where there is not a protrusion is about 0.004 inches. As mentionedabove, the protrusions preferably extend at least 0.002 inches so thatthey can sufficiently grip into patient tissue. Such extension of theprotrusions is that which is beyond the underlying thickness of thematerial 104. The protrusions are preferably separated from one anothera sufficient distance such that the voids formed between the protrusionsallow patient tissue to occupy these voids to reduce the tendency forthe therapeutic member, and the radioactive source 102 therein, tomigrate or rotate. Preferably, these voids or spaces between protrusionsare at least 0.010 inches, so that patient tissue can fit into thesespaces. The overall dimensions of the therapeutic members of the presentinvention are limited by the inner diameter of the needle that is to beused to implant the members. For example, the larger the inner diameterof the needle, the more the protrusions can extend.

The term polymer, as used herein, is also meant to include copolymers.Table 2 below provides examples of bioabsorbable polymers suitable foruse in producing embodiments of the present invention, along withspecific characteristics (e.g., melting points) of the various polymers.A further discussion of such bioabsorbable polymers can be found in anarticle by John C. Middleton and Arthur J. Tipton entitled “SyntheticBiodegradable Polymers as Medical Devices,” published Mar. 1998 inMedical Plastics and Bio-materials, which article is incorporated hereinby reference.

TABLE 2 Biodegradable polymers, properties and degradation time MELTINGGLASS- DEGRADA- POINT TRANSITION MODULUS TION TIME POLYMER (° C.) TEMP(° C.) Gpa)^(a) (MONTHS)^(b) PGA 225-230 35-40 7.0  6 to 12 LPLA 173-17860-65 2.7 >24 DLPLA Amorphous 55-60 1.9 12 to 16 PCL 58-63 (−65)-(−60)0.4 >24 PDO N/A (−10)-0     1.5  6 to 12 PGA-TMC N/A N/A 2.4  6 to 1285/15 Amorphous 50-55 2.0 5 to 6 DLPLG 75/25 Amorphous 50-55 2.0 4 to 5DLPLG 65/35 Amorphous 45-50 2.0 3 to 4 DLPLG 50/50 Amorphous 45-50 2.0 1to 2 DLPLG ^(a)Tensile or flexural modulus. ^(b)Time to complete massloss. Rate also depends on part geometry.

FIG. 9 illustrates an exemplary applicator 900, often referred to as aMICK™ applicator, that can be used to implant the therapeutic members ofthe present invention at variable spaced locations within a patient'sbody. Such an applicator 900 is available from Mick Radio-NuclearInstruments, Inc., of Mount Vernon, N.Y.

The applicator 900 includes a hollow needle 912 insertable into thepatient's body, a needle chuck 913 for releasably holding the needle912, a magazine 914 for holding and dispensing therapeutic members ofthe present invention (containing seeds or other radioactive sources)into the needle chuck 913, a main barrel 916 connected to the needlechuck 913. Also shown in FIG. 9 is a stylet 917 extendable through themain barrel 916, the needle chuck 913, and a bore of the needle 912. Theapplicator 900 also includes a base frame member along which the needle912, the needle chuck 913, the magazine 914 and the main barrel 916 areslidably mounted. The frame member includes an abutment end 922 adaptedto abut a surface of the patient's body or a template (not shown) fixedwith respect to the body, a barrel collar 924 through which the mainbarrel 916 is slidable, and two rods 926 (only one can be seen in theside view of FIG. 9) extending between and fixedly attached to theabutment end 922 and the collar 924. The collar 924 is equipped with afinger ring 928 for receiving a finger of a user.

The applicator 900 is designed to allow the needle 912 to be moved indifferent increments with respect to the base frame. For this purpose,the main barrel 916 includes rows of detents or indentations 952 thatextend along the length of the barrel 916, with each row havingdifferent indentation spacing (only one row is shown in FIG. 9) Forexample, the applicator 900 can have a first row of indentations spacedat 3.75 mm, a second row of indentations spaced at 4.0 mm, a third rowof indentations spaced at 5.0 mm, a fourth row of indentations spaced at5.5 mm, and a fifth row of indentations at 6.0 mm. These spacings can bechanged as desired by using an applicator having a main barrel withother indentation spacings.

The barrel collar 924 includes a fixed portion 955 and a spacing dial956 rotatably mounted on the fixed portion 955. An operator can turn thedial 956 relative to the fixed portion 955 to select one of the rows orseries of indentations.

The magazine 914 includes a magazine head 933 and a cartridge 934 inwhich therapeutic members of the present invention can be stackedparallel to each other. A spring-loaded magazine plunger 938 is biasedagainst the therapeutic members (each of which includes a radioactivesource 102) at the upper end of the magazine 914 to facilitate movementof the therapeutic members into the needle chuck 913 and to provide anindication to the operator that a therapeutic member has been dispensedfrom the cartridge 934.

The cartridge 934 can be preloaded with a plurality of therapeuticmembers of the present invention (e.g., up to 20 members, each with aradioactive source 102) and then screwed into the magazine head 933. Thecartridge 934 can be keyed to the needle chuck 913 to prevent itsincorrect insertion into the needle chuck 913.

In the operation, the needle 912 is inserted into a patient in an areawhere a single radioactive source or row of radioactive sources is to beimplanted. Then, the needle chuck 913 of the body of the applicator 900is coupled with the protruding end of the needle 912 to prepare theapplicator 900 for use. An initial radioactive source spacing can be setby adjusting the spacing dial 956 to select a particular row ofindentations 952 on the main barrel 916 corresponding to the desiredspacing. The stylet 917, which is initially fully extended in the needle912, is then retracted from the needle 912 and the needle chuck 913,enabling a therapeutic member (including a radioactive source) from themagazine 914 to be positioned in the chuck 913 for movement into theneedle 912. When the style 917 is retracted, the therapeutic member ismoved into the chuck and the extended magazine plunger 938 will movefurther into the magazine 914, which will indicate to the operator thata member has been positioned for transfer into the needle 912. Thestylet 917 is then pushed through the barrel 916 against the therapeuticmember, forcing the member through the needle 912 and into the patient'sbody.

After a first member (including a radioactive source) has beenimplanted, the needle 912 is withdrawn from the patient's body by aparticular distance so that the next radioactive source to be implantedis spaced apart from the first radioactive source. Then, the stylet 917is again retracted to enable the next therapeutic member (with aradioactive source) from the magazine 914 to be positioned for movementinto the needle 912. The stylet 917 is then advanced through the needle912 to force the therapeutic member into the patient's body at a desireddistance away from the first member. This procedure is repeated forsubsequent therapeutic member implants. Additional details of thisprocess and the applicator 900 can be found in U.S. Pat. No. 5,860,909,which is incorporated herein by reference. This is just one example of adevice that can be used to implant therapeutic members of the presentinvention. Other devices may also be used, while still being within thescope of the present invention. For example, rather than usingcartridges as described above, therapeutic members of the presentinvention (and optionally, spacers therebetween) can be preloaded into aneedle that is used to implant a row of such members (and optionally,spacers therebetween) in a single needle track.

The conventional stylet 917 that is used with an applicator, such as aMick™ applicator, is made using a solid wire. However, this can resultin the mislocation of the sources in the needle track due to vacuumphenomena occurring as the needle and stylet are withdrawn. To overcomethis problem, the stylet 917 is preferably a vented stylet that includesa vent that extends the length of the stylet, as described in U.S. Pat.No. 6,554,760, which is incorporated herein by reference.

Embodiments of the present invention, as described above, are directedto therapeutic members that include protrusions and/or anchor mechanismsthat reduce the tendency for the therapeutic member and the radioactivesource therein to migrate and rotate within a patient's body afterimplantation. Embodiments of the present invention are also directed tocartridges, similar to 934, that are pre-loaded with such therapeuticmembers.

The above mentioned embodiments of the present invention relate totherapeutic members that include a single radioactive source (a singleseed, rod or coil). It is also possible that embodiments of the presentinvention can be used together with elongated members known as strandsthat include multiple radioactive sources that are spaced from oneanother, e.g., as described in U.S. patent application Ser. No.10/035,083, which was filed on Dec. 28, 2001, and which is incorporatedherein by reference. More specifically, one or more therapeutic memberas described in FIGS. 1-7, which each include a single radioactivesource 102, can be used together with one or more strand that includesmultiple radioactive sources.

For example, a single needle can be loaded with a therapeutic memberhaving a single radioactive source as well as with a strand havingmultiple radioactive sources, thereby allowing for implantation of bothduring the same procedure that include insertion and removal of theneedle. This would be useful, e.g., where a first radioactive source ina row of radioactive sources is to be located near a patient's bladderor urethra. If a strand of radioactive sources were being implanted, andthe end of the strand were inserted too far and into the patient causingit to enter the bladder or urethra, then the entire strand would have tobe removed from the patient. However, if the first radioactive sourceimplanted was within a therapeutic member of the present invention, andthat radioactive source got into the bladder or urethra, then it wouldbe possible to remove the single first radioactive source withoutremoving strand that followed the first radioactive source.

As mentioned above, seeds (or other radioactive sources) are sometimesimplanted into a patient by preloading a hollow needle with seeds andspacers that are used to maintain a desired distance between a row ofseeds, e.g., as described in U.S. Pat. No. 6,554,760, which isincorporated herein by reference. The seeds and spacers are deployedfrom the hollow needle using a stylet, which preferably includes aradial vent that extends the length of the stylet, to reduce themislocation of the radioactive sources in the needle track due to vacuumphenomena occurring as the needle and stylet are withdrawn. In suchimplants, the first and last seeds are the most likely seeds to migrateand/or rotate, however the other seeds, as well as the spacers, may alsomigrate and/or rotate within the needle track. To reduce migration ofthe seeds, therapeutic members of the present invention can be used.That is, a seed can be encapsulated by a material that includesprotrusions that will resist the migration and rotation of the seedtherein. In another embodiment, protrusions can be added to the spacersthat are used to maintain the desired distances between the radioactivesources. Such spacers with protrusions can be made in manners similar tothose explained above. For example, protrusions can be added topreexisting spacers (e.g., cylindrical spacers) by encapsulating thespacer with a material within which protrusions are formed.Alternatively, spacers can be manufactured to include protrusions. Suchspacers can be formed, e.g., using an embossing mold, or by machining,crimping or otherwise forming protrusions in an outer surface of thespacers. The spacers with protrusions can be used together withtherapeutic members having protrusions, or with radioactive sources thatdo not have protrusions. When used with radioactive sources not havingprotrusions, the spacers with protrusions would preferably be located atboth longitudinal ends of the radioactive sources, to thereby trap theradioactive sources in place. For example, if five radioactive seedswere to be implanted in a single needle track, six such spacers can beused (i.e., four spacers each of which separate pairs of seeds, and aspacer prior to the first seed, and a spacer following the last seed).The spacers that are located between seeds preferably includeprotrusions similar to those explained with reference to FIGS. 1-7. Thespacers that are located prior to the first seed and following the lastseed in the needle track can include protrusions similar to thoseexplained with reference to FIGS. 1-7, or can include anchor mechanismssimilar to those described above with reference to FIGS. 8A-8D. Thespacers with protrusions can be made entirely from a bioabsorbablematerial, examples of which are listed above. Alternatively, the spacerswith protrusions can be made from a non-bioabsorbable material which isbiocompatible. In still another embodiment, the spacer is made of a bodythat is biocompatible but non-bioabsorbable, which is encapsulatedwithin a bioabsorbable material that is used to form the protrusions.

FIGS. 10A-10C illustrate a spacer 1000 according to another embodimentof the present invention. As shown in FIGS. 10A-10C, the spacer 1000includes two halves 1002 and 1004 that are connected by a living hinge1006. The halves 1002 and 1004 are shown as being half cylinders, butother shapes are also possible. The living hinge 1006 is biased suchthat after the spacer is folded into its closed position (FIG. 10B), thespacer tends to open up such that a gap 1008 forms between the twohalves (FIG. 10C). This can be accomplished, e.g., by molding the twohalves 1002 and 1004 and the living hinge 1006 in the open positionshown in FIG. 10A. The two haves 1002 and 1004 can then be folded towardone another along the living hinge 1006 to place the spacer 1000 in theclosed position shown in FIG. 10B, at which point the spacer can beinserted into a hollow needle used to implant spacers and radioactivesources in a patient. Once implanted in the patient, the spacer 1000will tend to open or unfold along the living hinge 1006, causing anouter surface of the spacer 1000 to thereby engage the patient tissuethat surrounds the spacer 1000. This engagement with patient tissue willcause the spacer to resist migration and rotation. To further resistmigration and rotation, protrusions, such as those discussed above, canbe added to the outer surface of the spacer. The spacer 1000 can be madeentirely from a bioabsorbable material, examples of which are listedabove. Alternatively, the spacer 1000 can be made from anon-bioabsorbable material which is biocompatible.

In accordance with other embodiments of the present invention, an entirestrand 1100 that includes multiple radioactive sources (e.g., seeds)102, or portions of the strand 1100, can include the protrusions of thepresent invention, e.g., as shown in FIG. 11. Because a typical strandincludes polymeric material that attaches multiple radioactive sourcesto one another at desired spacings, a strand is not as susceptible tomigration and twisting as loose radioactive sources. Nevertheless, it isstill possible that that radioactive sources within the strands,especially the radioactive sources located near the distal ends of thestrand, can migrate and/or twist. By including protrusions that extendfrom the strand, the tendency for the strand or portions of the strandto migrate and/or twist can be reduced. Such protrusions can extend fromportions of the strand where radioactive sources are located, but canalternatively or additionally extend from other portions of the strand,such as the portions of the strand between the radioactive sources.

In another embodiment of the present invention, the anchor mechanism(e.g., 810) disclosed above with reference to FIGS. 8A-8E can be locatedat one or both longitudinal distal ends of a strand 1200 that includesmultiple radioactive sources 102, e.g., as shown in FIG. 12.

The strands 1100 and 1200 can be manufactured using similar moldingprocesses that were used to produce the therapeutic members of thepresent invention. For example, to produce the strand 1100, radioactivesources 102 can be placed into an embossing mold that allows theradioactive sources 102 to be spaced at the appropriate intervals in acavity of the embossing mold that is shaped to the desired finaldimensions, including the protrusions, of the strand. All the spacingsbetween the radioactive sources 102 can be of different lengths, if thepreoperative therapeutic plan so specifies. Spacers (not shown) can beplaced between radioactive sources 102 to keep a desired spacing betweenthe radioactive sources, if desired. Alternative means for maintainingthe spacings between adjacent radioactive sources may be used, as isknown in the art. The strand 1200 can be manufactured in a similarfashion as was just described, and as was described above with referenceto FIGS. 8A-8E.

In accordance with specific embodiments of the present invention, aresulting strand (e.g., 1100 or 1200) is a single solid monofilament ofa polymer with the radioactive sources 102 spaced within themonofilament and encapsulated at the appropriate intervals. The strandis preferably axially flexible. However, the strand preferably hassufficient column strength along its longitudinal axis so that thestrand can be urged out of a hollow needle without the strand foldingupon itself. Again, the intervals can be selected to be any distance orcombination of distances that are optimal for the treatment plan of thepatient.

In another embodiment, a strand can be made by inserting (i.e., pushing)radioactive sources and spacers through an opening in one end of anelongated hollow tube of bioabsorbable material. Additional details of aseed pusher that can be used in this process are described in U.S. Pat.No. 6,761,680, which was incorporated herein by reference above. Theprotrusions of the present invention can be formed on the outer surfaceof the hollow tube prior to or after the insertion of the radioactivesources and spacers.

In a further embodiment, a strand can be constructed using a pair ofpreformed elongated members of bioabsorbable material that are shapedlike half-shells, as described in U.S. Pat. No. 6,761,680, which isincorporated herein by reference. The two half-shells can be separatefrom one another. Alternatively, the two half shells can be connected bya living hinge along their length. The radioactive sources and spacersare placed within a first one of half-shells. The second half-shell isthen mated with the first half-shell, and the half-shells are fusedtogether (e.g., using ultrasonic welding or heat), thereby fixing theradioactive sources and spacers inside. The protrusions of the presentinvention can be formed on the outer surface of such half-shells beforeor after the radioactive sources and spacers are placed therein.

In still another embodiment, a strand can be made by inserting the seedsand spacers into a tube of braded bioabsorbable material. Additionaldetails of such a braded bioabsorbable tube are described in U.S. Pat.No. 5,460,592, which is incorporated herein by reference. Protrusionscan then be added, e.g., by slipping doughnut shaped rings over thebreaded material. Such doughnut shaped rings can also be slipped overany other type of strand that has a generally cylindrical outer surface.

In another embodiment, one or more spacers 1000 that are biased to open(as described above with reference to FIG. 10) can be incorporated intoa strand 1300, as shown in FIG. 13. The spacers 1000 can be incorporatedinto the strand 1300 in various manners, such as by insert molding theminto the strand. When the strand 1300 including such spacers 1000 isinserted into a hollow needle, the spacers 1000 will be kept in theirclosed position by the inner wall of the needle. However, once implantedin a patient, the spacers 1000 will at least partially open and engagethe tissue surrounding the spacer, thereby anchoring the entire strand1300. More generally, portions of the strand 1300 can be biased suchthat they at least partially open or expand to engage tissue surroundingthe strand. As shown in FIG. 13, the portions of the strand that open toengage surrounding tissue can be at one or both distal ends of thestrand and/or at locations between the distal ends. In FIG. 13, theliving hinges 1006 are shown as being along the length of the strand1300. However, this need not be the case. For example, a living hingecan be located at one or both of the longitudinal ends of the strand,and thus be perpendicular to the length of the strand.

Embodiments of the present invention are also directed to radiopaquemarkers that include protrusions and/or anchor mechanisms, similar tothose described above, to reduce the tendency of the markers to migrateand rotate within a patient's body after implantation. Such markers canbe made entirely or partially of a radiopaque material. Such aradiopaque material is often a dense, high atomic number material, suchas gold or tungsten, which can block the transmission of X-rays or otherradiation so that the markers can be detected using X-ray or otherradiation imaging techniques. For example, a marker can be a ball, rodor wire constructed from gold or tungsten. Alternatively, the marker canbe a container that includes a ball, rod or wire of radiopaque material,or a container at least partially coated with a radiopaque material. Onecommercially available marker is marketed under the trademark VISICOILand is available from RadioMed Corporation of Tyngsboro, Mass. These arejust a few examples of such markers. One of ordinary skill in the artwill understand that other markers are also possible. To add theprotrusions and/or anchor mechanisms to an existing marker, the markercan be encapsulated in a polymeric material within which protrusionsand/or anchor mechanisms are formed, in any of the manners describedabove. Alternatively, a marker can be manufactured to includeprotrusions and/or anchor mechanisms.

The markers can be implanted within a patient that will be undergoingexternal beam radiation therapy. If the patient is to also undergobrachytherapy, then the markers can implanted at the same time thatradiation sources are being implanted into the patient. In specificembodiments, radiopaque markers can be included in spacers and/orstrands of the present invention. By including a marker within a spaceror strand that includes protrusions and/or anchor mechanisms, the markertherein will also be resistant to migration and rotation.

In another embodiment, shown in FIGS. 14A-14D, an anchor mechanism 1400includes a sleeve 1404 to which are attached, by living hinges 1406,wings 1408. The wings 1408 are shown as being generally rectangular, butcan have other shapes. Two wings 1408 are shown, but more are less canbe used. The sleeve 1404 is intended to be placed around an underlyingstructure 1402, which can be a radioactive source (e.g., seed, rod orcoil), a thermal ablation implant, a spacer, a strand, or a radiopaquemarker. Each living hinge 1406 is biased in its open position (FIGS. 14Aand 14B), such that after the wings 1408 are folded into their closedpositions (FIGS. 14C and 14D), the wings 1408 will tend to open. Thiscan be accomplished, e.g., by molding the anchor mechanism 1400 in theopen position shown in FIGS. 14A and 14B. After being placed around anunderlying structure 1402, the wings 1408 can then be folded inwardalong the living hinges 1406 to be in the closed position shown in FIGS.14C and 14D. When in the closed position, the entire structure,including the underlying structure 1402 and anchor mechanism 1400, canbe inserted into a hollow needle used to implant the structure in apatient. The inner wall of the hollow needle will keep the wings 1408 intheir closed position. Because of the biasing of the living hinges 1406,once implanted in the patient, the wings 1408 will tend to open orunfold along the living hinges 1406, causing the wings 1408 to therebyengage the surrounding patient tissue. This engagement will resistmigration and rotation of the structure 1402. To further resistmigration and rotation, protrusions, such as those discussed above, canbe added to the wings 1408 and/or sleeve 1404. The anchor mechanism 1400can be made entirely from a bioabsorbable material, examples of whichare listed above. Alternatively, the anchor mechanism can be made from anon-bioabsorbable material which is biocompatible.

In another embodiment, shown in FIGS. 15A-15B, an anchor mechanism 1500includes a sleeve 1504 from which extends a plurality of protrusions1506. The sleeve 1504 is intended to be placed around an underlyingstructure 1502, which can be a radioactive source (e.g., seed, rod orcoil), a thermal ablation implant, a spacer, a strand, or a radiopaquemarker, prior to implantation of the structure 1502. The protrusions1506 extending from the sleeve 1504 will reduce a tendency of theunderlying structure to migrate and rotate within a patient's body afterthe structure (with the anchor mechanism 1500 around it) is implanted.

A bore 1508 extends through the anchor mechanism 1500 to form the sleeve1504. In accordance with specific embodiments of the present invention,the shape of the bore 1508 is generally similar to the shape of theouter diameter of the underlying structure 1502. Thus, if the underlyingstructure 1502 is a cylindrical radioactive seed, the shape of the bore1508 is cylindrical, in accordance with specific embodiments.

In accordance with an embodiment, the inner diameter 1508 of the sleeve1504 (which is the outer diameter of the bore 1508) is sized so thatthere is an interference fit between the underlying structure 1502 andthe sleeve 1504. This can be accomplished by having the inner diameter1508 of the sleeve 1504 slightly smaller than the outer diameter of theunderlying structure 1502. Alternatively, the sleeve 1504 can be heatshrunk to tightly fit around the structure 1502. In another embodiment abiocompatible and preferably bioabsorbable adhesive can be used tosecure the sleeve 1504 to the underlying structure 1502. Othermechanisms of securing the sleeve 1504 to the structure 1502 are alsowithin the scope of the present invention. Where the underlyingstructure 1502 is an elongated strand (e.g., including a plurality ofradioactive sources along its longitudinal length), more than one anchormechanism 1500 can be placed around the strand, e.g., one slightlyinward from each longitudinal end of the strand.

The anchor mechanism 1500 can be made entirely from a bio-absorbablematerial, examples of which are listed above. Alternatively, the anchormechanism can be made from a non-bio-absorbable material which isbio-compatible.

In FIGS. 15A and 15B the protrusions 1506 are shown as being square orrectangular knobs that cause the outer surface of the anchor mechanism1500 to resemble a knobby tire. The protrusions 1506 can form aplurality of rows (e.g., four rows) which are regularly spaced about thesleeve 1504, e.g., with each row extending in a direction that is 90degrees from the adjacent rows. Alternatively, the protrusions canprotrude in a more random or irregular fashion.

Exemplary dimensions for one of the protrusions 1506 are0.010×0.008×0.003 inches. All of the protrusions 1506 can have similardimensions, or the dimensions of the protrusions may vary. For example,it is possible that the protrusions within a row have similardimensions, but the dimensions differ for different rows. For a morespecific example, another row of protrusions 1506 may have dimensions of0.006×0.005×0.002 inches. These are just a few examples. One of ordinaryskill in the art will appreciate from this description that theprotrusions can have other dimensions while being within the scope ofthe present invention.

Preferably, the protrusions 1506 extend at least 0.002 inches so thatthey can sufficiently grip into patient tissue (analogous to a knobbytire gripping soft dirt). The protrusions 1506 can extend radially fromthe sleeve 1504. For example, in the embodiments shown, the protrusions1506 extend in directions that are generally perpendicular to alongitudinal axis 1503 of the sleeve 1504 and the structure (e.g., seed)1502 therein. The protrusions 1506 may alternatively or additionallyextend at other angles with respect to the longitudinal axis 1503. Forexample, protrusions may extend at 45 degrees with respect to thelongitudinal axis 1503. In a specific embodiment, each half of thesleeve 1504 can have protrusions 1506 at a 45 degree angle facingtowards the middle of the sleeve 1504, or towards the ends of the sleeve1504. Various other angles, and combinations of angles, are alsopossible.

In another embodiment, the protrusions of the anchor mechanism can becylindrical (e.g., similar to as in FIG. 2), resemble bumps orsemi-spheres (e.g., similar to as in FIG. 3), triangular (similar to asin FIG. 4), or pyramidal (similar as in FIG. 5). These are just a fewexamples of the shapes of the protrusions. One of ordinary skill in theart reading this description would appreciate that other shapes are alsopossible. It should also be understood that an anchor mechanism of thepresent invention can include protrusions of numerous different shapes,including, but not limited to, the shapes discussed above. The variousprotrusions are shown as having a common orientation, but can havedifferent orientations.

In a further embodiment, shown in FIGS. 15C and 15D, the protrusions ofthe anchor mechanism 1500 are ribs 1506′ that encircle the sleeve 1504.Two ribs 1506′ are shown in FIGS. 15C and 15D. However, it should beunderstood that more or less ribs 1506′ can be included. It should alsobe understood the ribs can be helical (i.e., spiral). In one specificembodiment, the ribs can form counter balancing screw threads (i.e.,opposing helixes). For example, the threads on one half of the membercan be right hand threads, while the threads on the other half of themember can be left hand threads.

In another embodiment, the plurality of protrusions can form anirregular pattern on the outer surface of a sleeve 1504.

It is preferred that the anchor mechanism 1500 is placed about theunderlying structure 1502 so that a portion of the underlying structure1502 extends from each longitudinal end of the anchor mechanism 1500, asis the case in FIGS. 15A-15D. This reduces the chances that the anchormechanism 1500 will become separated from the underlying structure 1502.In other words, it is preferred that the anchor mechanism 1500 not beattached to just one longitudinal end of the underlying structure 1502,which would increase the possibility that the anchor mechanism 1500 mayseparate from the underlying structure 1502, e.g., if the underlyingstructure slips out. Also, where the anchor mechanism 1500 does notextend from one of the longitudinal ends of the underlying structure1502, the anchor mechanism 1500 does not lengthen the underlyingstructure 1502. This is beneficial in that the anchor mechanism will notaffect the depths at which the underlying structure can be implanted,nor will it affect the distances that can be achieved between a pair ofunderlying structures (e.g., a pair of radioactive seeds). Additionally,this will allow for more precise placement of the structure 1500 duringimplantation.

For a portion of the underlying structure 1502 to extend from eachlongitudinal end of the anchor mechanism 1500, the longitudinal lengthof the anchor mechanism 1500 (i.e., the length of the sleeve 1504)should be less than the length of the underlying structure 1502.Additionally, for a portion of the underlying structure 1502 to extendfrom each longitudinal end of the anchor mechanism 1500, the bore 1508should extend the entire length of the anchor mechanism.

In accordance with specific embodiments of the present invention, wherethe underlying structure is a radioactive seed, a plurality ofradioactive seeds, with an anchor mechanism 1500 of the presentinvention fit around each of the seeds (or at least some of the seeds),can be loaded into a cartridge. Examples of such a cartridge (e.g., 934)were discussed above with reference to FIG. 9. This would enable theseeds, with the anchor mechanisms 1500 fit around them, to be implantedinto patient tissue using an applicator, such as applicator 900described with reference to FIG. 9.

Embodiments of the present invention are also directed to therapeuticmembers for use in brachytherapy and other radiation treatment. Inaccordance with an embodiment such a therapeutic member includes anunderlying structure (e.g., a radioactive source, a thermal ablationimplant, a spacer, a strand or a radiopaque marker), with a sleeve tofit around the structure. The sleeve has a bore that extends an entirelongitudinal length of the sleeve, and through which the structure fits,such that a portion of the structure extends out from each longitudinalend of the sleeve. One or more protrusion extends from the sleeve forengaging the patient tissue after implantation of the therapeuticmember, to thereby reduce a tendency for the therapeutic member tomigrate and rotate after implantation.

The previous description of the preferred embodiments is provided toenable any person skilled in the art to make or use the embodiments ofthe present invention. While the invention has been particularly shownand described with reference to preferred embodiments thereof, it willbe understood by those skilled in the art that various changes in formand details may be made therein without departing from the spirit andscope of the invention.

1. An anchor mechanism adapted to reduce a tendency for a structure tomigrate and rotate after implantation of the structure into a patient,where the structure is one or more of a radioactive source, a thermalablation implant, a spacer, a strand and a radiopaque marker, the anchormechanism comprising: a sleeve adapted to fit around the structure; saidsleeve having a bore that extends an entire longitudinal length of saidsleeve, and through which the structure fits, such that a portion of thestructure extends out from each longitudinal end of said sleeve; and twoor more protrusions extending from an outer surface of said sleeve alongat least a portion of the longitudinal length of said sleeve, said twoor more protrusions each having a substantially squared profile formedby sidewalls extending along a portion of the longitudinal length andalong a portion of a circumference of said sleeve, to form a spacebetween said protrusions, at least along the longitudinal length of saidsleeve, to receive surrounding patient tissue upon implantation of thestructure into a patient, to thereby reduce a tendency for the structureto migrate and rotate after implantation; wherein the sidewalls fromadjacent protrusions that form the space along the longitudinal lengthof the sleeve are about parallel to each other and substantiallyperpendicular to the longitudinal axis of the sleeve; wherein athickness of said sleeve varies such that the thickness is greater wherethere are said two or more protrusions than where there is not aprotrusion.
 2. The anchor mechanism of claim 1, wherein an innerdiameter of said sleeve is slightly smaller than an outer diameter ofthe structure so that an interference fit is provided therebetween. 3.The anchor mechanism of claim 1, wherein said sleeve is adapted to beheat shrunk to the structure.
 4. The anchor mechanism of claim 1,wherein said sleeve is adapted to be adhered to the structure.
 5. Theanchor mechanism of claim 1, wherein said sleeve and said two or moreprotrusions are bioabsorbable.
 6. The anchor mechanism of claim 1,wherein said sleeve and said two or more protrusions are biocompatible.7. A therapeutic member for use in brachytherapy and other radiationtreatment, comprising: a structure that is one or more of a radioactivesource, a thermal ablation implant, a spacer, a strand and a radiopaquemarker; a sleeve to fit around said structure; said sleeve having a borethat extends an entire longitudinal length of said sleeve, and throughwhich the structure fits, such that a portion of the structure extendsout from each longitudinal end of said sleeve; and two or moreprotrusions extending from an outer surface of said sleeve along atleast a portion of the longitudinal length of said sleeve, said two ormore protrusions each having a substantially squared profile formed bysidewalls extending along a portion of the longitudinal length and aportion of a circumference of said sleeve, to form a space between saidprotrusions, at least along the longitudinal length of said sleeve, toreceive surrounding patient tissue upon implantation of the structureinto a patient, to thereby reduce a tendency for the structure tomigrate and rotate after implantation; wherein the sidewalls fromadjacent protrusions that form the space along the longitudinal lengthof the sleeve are about parallel to each other and substantiallyperpendicular to the longitudinal axis of the sleeve; wherein athickness of said sleeve varies such that the thickness is greater wherethere are said two or more protrusions than where there is not aprotrusion.
 8. The therapeutic member of claim 7, wherein said structurecomprises said strand that includes a plurality of radioactive sources.9. The therapeutic member of claim 7, wherein an inner diameter of saidsleeve is slightly smaller than an outer diameter of said structure sothat an interference fit is provided therebetween.
 10. The therapeuticmember of claim 7, wherein said sleeve is heat shrunk to said structure.11. The therapeutic member of claim 7, wherein said sleeve is adhered tosaid structure.
 12. The therapeutic member of claim 7, wherein saidsleeve and said two or more protrusions are bioabsorbable.
 13. Thetherapeutic member of claim 7, wherein said sleeve and said two or moreprotrusions are biocompatible.
 14. A method for use in brachytherapy andother radiation treatment, comprising: providing a structure that is oneor more of a radioactive source, a thermal ablation implant, a spacer, astrand and a radiopaque marker; fitting a sleeve around the structuresuch that a portion of the structure extends out from each longitudinalend of the sleeve, wherein the sleeve includes two or more protrusionsextending from an outer surface of said sleeve along at least a portionof the longitudinal length of said sleeve, said two or more protrusionseach having a substantially squared profile formed by sidewallsextending along a portion of the longitudinal length and along a portionof a circumference of said sleeve, to form a space between saidprotrusions, at least along the longitudinal length of said sleeve;wherein the sidewalls from adjacent protrusions that form the spacealong the longitudinal length of the sleeve are about parallel to eachother and substantially perpendicular to the longitudinal axis of thesleeve; loading the structure, with the sleeve around the structure,into a hollow needle; and using the hollow needle to implant thestructure, with the sleeve around the structure, into patient tissue;wherein the patient tissue is caught in the at least one said space uponimplantation of the structure, with the sleeve around the structure, tothereby reduce a tendency for the structure to migrate and rotate atimplantation; and wherein a thickness of said sleeve varies such thatthe thickness is greater where there are said two or more protrusionsthan where there is not a protrusion.
 15. An anchor mechanism to reducea tendency for a structure to migrate and rotate after implantation ofthe structure into a patient, where the structure is at least one of aradioactive source, a thermal ablation implant, a spacer, a strand and aradiopaque marker, the anchor mechanism comprising: a sleeve adapted tofit around the structure such that ends of the structure are notcovered; said sleeve having a bore that extends an entire longitudinallength of said sleeve; two or more protrusions extending from an outersurface of said sleeve, said two or more protrusions each having asubstantially squared profile formed by sidewalls extending along aportion of the longitudinal length and along a portion of acircumference of said sleeve; one or more spaces formed by the two ormore protrusions that extend along at least a portion of thelongitudinal length of said sleeve; and wherein the sidewalls fromadjacent protrusions that form the space along the longitudinal lengthof the sleeve are about parallel to each other and substantiallyperpendicular to the longitudinal axis of the sleeve; said sleeveadapted to be received upon an implantation site such that patienttissue is caught in the one or more spaces at implantation to therebyreduce a tendency for the structure to migrate and rotate atimplantation; wherein a thickness of said sleeve varies such that thethickness is greater where there are said two or more protrusions thanwhere there is not a protrusion.